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Approach to Infertility - Introduction
 
     Infertility is a disorder that affects 10 - 15% of couples. The standard and time-honored definition of infertility is "failure to achieve a pregnancy after one year of unprotected intercourse". However this standard definition may be inadequate for all patients. For example couples with obvious problems and older couples may need to be considered for earlier evaluation. When counseling infertile couples, it is also useful to remember that the chance that a pregnancy will happen every month, in normal couples is only about 25% and that most treatment options in infertility do not exceed this pregnancy rate.

     The basic evaluation of an infertile couple begins with a good history and physical examination. Obtaining a sexual history helps identify any sexual dysfunction, which the couple may not volunteer. Following this one needs to do a semen evaluation, assess tubal patency and assess ovulation.
 
Evaluating the male factor
 
     The semen analysis is the gold standard for the evaluation of male infertility. It is a relatively easy and inexpensive test to obtain. While ordering a semen analysis, it is important to ensure that there is abstinence for a period of 4 days prior to the test. It is best that the collection is done at the place of testing. If this is not possible then the sample must reach the lab within 30 - 60 minutes of collection. In the event that a condom is required for collection, one without spermicide must be used. These are special condoms and not ones that are usually avaiablebe. If an abnormal semen analysis is found then the test must be repeated at least 4 weeks after the first test. If the abnormal result persists then consideration for referral to an urologist must be made. An anatomical and endocrine assessment needs to be made. Though various treatment modalities have been tried, in general hormonal treatment does not improve the fertility potential.
 
Evaluating the female factor
 
Assessing ovulation:
     The methods of assessing ovulation vary from basal body temperature charts to hormonal assays to ultrasound assessment of follicular growth. Basal body temperature charts are inexpensive but are ineffective in prospectively predicting ovulation. Mid-luteal phase progesterone is simple for patients to obtain and give a general assessment of ovulation and adequacy of luteal phase. The disadvantages are that the levels vary with different cycles and it does not give any assessment of the endometrium. Endometrial biopsies in the late luteal phase were considered the gold standard for the evaluation of luteal phase. Unfortunately the interpretation may not be consistent and it needs to be done twice to establish luteal phase inadequacy. This becomes painful and expensive.

     Serial ultrasounds and follicular tracking is very predictive of ovulation and also helps assess endometrium but is expensive. Doing the monitoring on just 2 - 3 days to helps establish growth of the follicle and document ovulation rather than scans on done every day or every alternate day will help decrease the total number of scans done and also decrease the inconvenience for the patient.
 
Uterotubal assessment:
     There are many ways of doing an uterotubal assessment. These include an HSG, laparoscopy, Hysteroscopy and Sonosalpingography. The age old outpatient "tube testing" with the Rubin's canula may still have a very limited place in certain situations where cost primarily becomes an issue or if a more definitive test like a laparoscopy is consciously postponed while assessing ovulation or the male factor.

     The HSG is the initial choice for uterotubal assessment. This provides a screening for the endometrial cavity and also assesses tubal patency. Although there may be artifactual filing defects or tubal spasm, the HSG remains critical in the initial evaluation of an infertile woman.

     A laparoscopy is an extremely useful test in the sense that it helps evaluate the adnexae along with documenting tubal patency. It helps identify and treat endometriosis and adhesions, which may be contributing to the infertility. It is inevitably done later in the course of any infertility work up. It may be useful to combine a hysteroscopy with a laparoscopy if assessment of the uterine cavity is also needed in some patients.

     More recently the sonohysterogram and the sonosalpingogram are increasingly used. These are relatively non-invasive ways of testing for tubal patency.
 
PCT is there a role?
 
     The post coital test is a method of assessing the cervical mucus (as an indictor of ovulation) and the sperm survival and motility. Today, most people consider it a redundant test since IUI is the treatment option resorted to earlier than later in most situations. Still it has place in certain situations and also helps to give us an idea about sexual dysfunction in a couple.
 
Handling anovulation
 
     The initial evaluation of anovulation includes a TSH and a prolactin level. In older women a FSH value is also important to look at ovarian reserve. If these are normal then treatment is initiated with clomiphene citrate, starting with a dose of 50 mg between day 2 - 5 of the cycle and then increasing if there is no response. At least the first cycle of clomiphene needs to be monitored to evaluate response. In higher doses it is important that every cycle is monitored by ultrasound.

     In women who have an elevated TSH or Prolactin, appropriate work up and treatment will usually result in anovulation. Some times after correction of the underlying problem, clomiphene may be needed to induce ovulation.
 
What do we do with clomiphene failure?
     If there is no response to clomiphene, then one needs to assess presence or absence of insulin resistance. Insulin resistance is also tested earlier in hyperandrogenic women. If there is a suggestion of insulin resistance, then there may be value in considering therapy with metformin at a dose of 500 mg three times a day to decrease the insulin resistance. This may be used in addition to clomiphene in such women.

     The alternate therapy in these women ( or in women who do nto respond to Clomiphene + metformin) is to use gonadotropins. The dosage of gonadotropins required to induce ovulation may vary from patient to patient. It is mandatory that all gonadotropin cycles be monitored with ultrasound.

     Anovulatory women who need gonadotropins must have tubal patency assessed before therapy is initiated. Given the cost of therapy, if there were no pregnancy in a 2-3 cycles then it would be worthwhile to consider IUI in such patients.
 
Managing male infertility
 
     The management options in the presence of significant abnormality in the semen analysis would be intrauterine insemination, donor insemination and ICSI.

     For optimising success with IUI, at least 1 million sperms need to be inseminated. In oligospermic samples this may be achieved by combining 2 samples. Superovulation increases the chances of pregnancy with IUI.

     While offering donor insemination, it is important to stress to the couple that success rates may vary from 5 - 20 %. It is important to maintain anonymity, match donors and ensure effective screening for infections and disease.
 
Offering ART
 
     Referral for ART is done in the following situation:

     Tubal factors
     Male factor
     Unexplained infertility
     Severe endometriosis
     Premature ovarian failure - (donor oocyte IVF)

     It cannot be emphasised enough that couples must be counselled well prior to IVF or ICSI and be given realistic expectations of outcome.
 
When do we stop?
     We have to consider stopping therapy if there is no successful outcome after 3 or more years of treatment, if all treatment options are exhausted or if cost becomes a constraining factor.

     In these situations providing emotional support and directing to think of adoption may be more realistic options.

     Infertility is an emotional and social problem as much as it is a medical problem. Couples must therefore be approached gently, treatment planned rationally and care taken to not perpetuate myths.